Mechanism research on the treatment of gout with modified Simiao decoction based on network pharmacology and Mendelian randomization method

The treatment of gout remains a huge challenge, and currently, the mainstream Western medicine treatment methods still have some drawbacks. This study aims to elucidate the potential mechanism of modified Simiao decoction (MSMD) in the treatment of gout through network pharmacology analysis, Mendelian randomization (MR), and molecular docking. We hope to contribute to the research on the targets of action of traditional Chinese medicine and the exploration of the mechanism of gout. We employed network pharmacology to screen the potential targets of MSMD in relation to gout. MR was utilized to further augment the potential targets and elucidate the causal associations between them and gout. Eventually, the identified targets were combined with active ingredients for the purpose of molecular docking. Through network pharmacology, we identified 44 potential targets. MR analysis identified 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) as a potential causal risk factor for gout (odds ratio [95% confidence interval] = 1.192 [1.033-1.375], P = .016). Molecular docking predicted that TP53, IL6, TNF, peroxisome proliferator-activated receptor γ, IL1B, and HMGCR exhibited favorable binding effects with the active ingredients. TP53, IL6, TNF, peroxisome proliferator-activated receptor γ, and IL1B are central inflammatory targets of MSMD. Notably, HMGCR was identified as a causal risk factor for gout and a potential target of MSMD. We hypothesize that MSMD may exert therapeutic effects by inhibiting HMGCR activity, counteracting its risk effect. This hypothesis, along with the anti-inflammatory roles of other targets, warrants further experimental validation.